Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys.
Differential release of extracellular vesicle tRNA from oxidative stressed renal cells and ischemic kidneys.
复制标题
氧化应激肾细胞和缺血肾细胞细胞外囊泡tRNA的差异释放。
DOI：
10.1038/s41598-022-05648-3
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发表时间：
2022-01-31
影响因子：
4.6
通讯作者：
Kwon SH
中科院分区：
文献类型：
--
作者：
Lee HK;Lee BR;Lee TJ;Lee CM;Li C;O'Connor PM;Dong Z;Kwon SH
虽然基于尿液的液体活检已扩展到细胞外核酸的分析，但尚未探索包封在细胞外囊泡内的转移RNA（tRNA）作为肾损伤的一类新的尿液生物标志物的潜力。使用大鼠肾脏和小鼠肾小管细胞损伤模型，我们测试了细胞外囊泡装载的tRNA及其m1A（N1-甲基腺苷）修饰是否反映了肾损伤的氧化应激，并确定了tRNA包装到细胞外囊泡中的机制。我们确定了一组细胞外囊泡加载，isoaccepting tRNA差异释放后，缺血再灌注损伤和氧化应激。接下来，我们发现，m1A修饰的细胞外囊泡tRNA，尽管增加了甲基化的tRNA在细胞内囊泡，氧化应激下表现出很少或没有变化。从机制上讲，氧化应激减少了tRNA加载到细胞内囊泡中，而由于囊泡从细胞表面的释放减少，加载tRNA的囊泡被积累。此外，Maf 1介导的转录抑制的tRNA降低货物的可用性细胞外囊泡释放响应氧化应激。总之，我们的数据支持细胞外囊泡tRNA的释放反映了肾小管的氧化应激，这可能有助于检测缺血性肾损伤，并可能导致氧化应激下蛋白质翻译的再平衡。
While urine-based liquid biopsy has expanded to the analyses of extracellular nucleic acids, the potential of transfer RNA (tRNA) encapsulated within extracellular vesicles has not been explored as a new class of urine biomarkers for kidney injury. Using rat kidney and mouse tubular cell injury models, we tested if extracellular vesicle-loaded tRNA and their m1A (N1-methyladenosine) modification reflect oxidative stress of kidney injury and determined the mechanism of tRNA packaging into extracellular vesicles. We determined a set of extracellular vesicle-loaded, isoaccepting tRNAs differentially released after ischemia–reperfusion injury and oxidative stress. Next, we found that m1A modification of extracellular vesicle tRNAs, despite an increase of the methylated tRNAs in intracellular vesicles, showed little or no change under oxidative stress. Mechanistically, oxidative stress decreases tRNA loading into intracellular vesicles while the tRNA-loaded vesicles are accumulated due to decreased release of the vesicles from the cell surface. Furthermore, Maf1-mediated transcriptional repression of the tRNAs decreases the cargo availability for extracellular vesicle release in response to oxidative stress. Taken together, our data support that release of extracellular vesicle tRNAs reflects oxidative stress of kidney tubules which might be useful to detect ischemic kidney injury and could lead to rebalance protein translation under oxidative stress.
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影响因子：
64.5
作者：
Goodarzi H;Liu X;Nguyen HC;Zhang S;Fish L;Tavazoie SF
通讯作者：
Tavazoie SF
DOI：
10.1152/ajprenal.2000.278.5.f758
发表时间：
2000-05-01
影响因子：
4.2
作者：
Bergin, E;Levine, JS;Lieberthal, W
通讯作者：
Lieberthal, W
活性氧/氧化应激导致小鼠短暂缺血损伤后肾脏纤维化恶化
DOI：
10.1152/ajprenal.90735.2008
发表时间：
2009-08-01
影响因子：
4.2
作者：
Kim, Jinu;Seok, Young Mi;Park, Kwon Moo
通讯作者：
Park, Kwon Moo
尿液外囊泡作为肾脏疾病中生物标志物的来源。
影响因子：
7.3
作者：
Gámez-Valero A;Lozano-Ramos SI;Bancu I;Lauzurica-Valdemoros R;Borràs FE
通讯作者：
Borràs FE
影响因子：
48
作者：
Cozen AE;Quartley E;Holmes AD;Hrabeta-Robinson E;Phizicky EM;Lowe TM
通讯作者：
Lowe TM